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Pharmacokinetics: What happens to THC in the body after ingestion?

Franjo Grotenhermen

The preferred forms of ingestion of cannabis preparations for medicinal use are inhalation (smoking cannabis flowers, vaporisation by vaporizer) and oral ingestion (cannabis-based medicines such as dronabinol/THC, Sativex, nabilone and hemp extracts). Less common are rectal use via homemade suppositories and external use on the skin.

Depending on the application, the absorption of THC into the blood, the distribution of THC in the body, the duration until the onset of the effect, the time of maximum effect, the duration of effect of THC, the degradation as well as the excretion of THC differ.

How much THC reaches the bloodstream?

When smoking, THC is detectable in the blood within a few seconds after the first puff, with maximum blood concentrations about five minutes after starting to smoke. About 10 to 35 percent of the THC in a cannabis cigarette reaches the bloodstream. This yield is influenced by the depth of inhalation, the duration of the puff and the length of time the air is held. Losses occur due to the destruction of part of the THC by combustion, side currents and incomplete absorption of THC by the mucous membrane of the respiratory tract. About 30 percent is lost through combustion. In a test with a vaporizer, it was found that on average about 35 percent of the inhaled THC was immediately exhaled again.

In the case of oral intake (eating, drinking), absorption is slow and uncertain. Maximum THC blood concentrations are generally found after 60 to 120 minutes. Part of the THC is broken down by gastric acid, but most is absorbed in the upper gastrointestinal tract and reaches the liver via the portal vein. In the liver, most of the THC is immediately broken down or metabolised, so that only 4 to 12 percent of the THC enters the entire bloodstream. However, some of the degradation products of THC have a similar effect to THC and contribute to the overall effect. This is especially true for the metabolic product 11-hydroxy-THC (11-OH-THC).

How much THC reaches the brain and other organs?

About 90 percent of the THC is found in the watery part of the blood after absorption, in the so-called blood serum. THC is predominantly bound to proteins there and thus flows through the blood vessels. There is only little "free THC" in the blood because THC is not very soluble in water.

Because of this poor water solubility but good fat solubility, the relationship between the THC concentration in the blood and the THC concentration in other body tissues, especially fat-rich tissues, changes relatively quickly. THC penetrates relatively quickly into tissues with good blood supply, including the liver, heart, lungs, muscles, spleen, kidneys and placenta.

Only about one percent of THC given intravenously, i.e. fully absorbed, is in the brain at the time of maximum mental effects. This relatively low concentration in the brain is probably due to the strong blood flow to the brain, which brings THC into the brain relatively quickly, but also out again quickly. It seems that the metabolite 11-hydroxy-THC enters the brain faster and achieves higher concentrations than THC itself. Since 11-hydroxy-THC is also psychoactive and is formed in the liver to a greater extent during oral intake (eating, drinking) than during inhalation, it can be assumed that this degradation product, especially during oral intake, contributes significantly to THC effects.

What is the course of the THC concentration in the blood?

Especially when it comes to blood tests in connection with driving ability, the significance of a certain THC concentration in the blood for the cannabis effect is of interest.

If THC is smoked or inhaled with a vaporiser, the course of the THC concentration in the blood plasma is similar to that after intravenous injection into the blood. Thus, in a study with several cannabis users, smoking a cannabis cigarette containing about 34 mg THC led to a maximum THC concentration in the blood plasma of about 160 ng/ml on average within a few minutes, with a wide range of variation between different participants. Within three to four hours, this concentration drops to a few nanograms per millimetre.

When taken orally, the THC concentration in the blood shows a flat course with maximum concentrations of about 5 to 10 ng/ml in the blood plasma after taking 20 mg THC. These maximum concentrations are reached after an average of one to two hours. However, especially after oral ingestion, the course of THC blood concentrations varies greatly in different persons and also in the same person. This concerns both the level of the concentrations and their course. It is not uncommon for the maximum concentration to be reached only after three or four hours.

In occasional users, THC can rarely still be detected in the blood above a concentration of 1 ng/ml after more than 12 or 24 hours. However, it does occur occasionally. In habitual users, however, detection after more than 24 hours or even after 48 hours is very common.